ISiCell: involving biologists in the design process of agent-based models in cell biology

Agent-based models are commonly used in biology to study tissue-scale phenomena by reproducing the individual behavior of the cells. They offer the possibility to study cellular biology at the individual cell scale to explore the basic behavior of cells which are responsible of the emergence of more complex phenomena at the tissue scale. Additionally, they can produce a predictive tool that will help taking decisions for biologic experiments based on in silico simulations. However these models require a good intercomprehension between the biologists and the modelers and thus it may take weeks or months to end up providing a usable prototype. To address this limitation, we propose a new methodology to facilitate the dialog between biologists and modelers and improve biologists’ involvement in the design of the model. For this purpose, UML diagrams, in particular, state-transition and activity diagrams, are used. They allow a better comprehension of the model for the biologists and offer a general frame for structuring models. Visualization of simulations is also used to have qualitative feedbacks from the biologist on the model. They are instrumental to validate or refine the prototype before exploring it. Alongside this methodology, we propose a web platform that enables to build state-transition and activity diagrams to describe a model and translate them into code. The generated code is then compiled on-the-fly and simulations are ready to visualize and explore. The platform also disposes of tools to directly visualize and manually explore the model. These tools allow for qualitative validation of the model and additional interaction with the biologists. Finally in this article, we show the capacity of our platform to reproduce models from the literature and to build new models starting from workshops with biologists. Its range of application is wide and includes immunology, oncology or cell biology. Author summary We developed a methodology based on diagrams to facilitate the dialog between computer scientists and biologists when building in silico models. The main idea is to limit misunderstandings and improve the involvement of the biologists in the prototyping process. For this purpose, we use visual methods to simplify the modeling phase. Alongside this methodology, we propose a web platform, called ISiCell, which enables to visually code thanks to diagrams that will be translated into code. The platform allows for compiling the generated code on the fly and to visualize and explore the model directly with the platform. The strong advantage of the platform is that one day workshop biologist/modeler allows to build new models. Additionally, we were able to reproduce models from the literature within the modeling platform showing the versatility of the tool. Our long-term objective is to use our methodology and platform in new contexts to develop new models. We intend the make the platform more user friendly in order to expand the community of users. Involving biologists in the conception of in silico models might improve their acceptability in the community.